Ex Parte Bruchez et al

Board of Patent Appeals and Interferences

Mar 18, 2008

10631573 (B.P.A.I. Mar. 18, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte MARCEL P. BRUCHEZ, HUGH R. DANIELS, STEPHEN A.
EMPEDOCLES, VINCE E. PHILLIPS, EDITH Y. WONG and DONALD
A. ZEHNDER
____________

Appeal 2008-1673
Application10/631,573
Technology Center 1600
____________

Decided: March 19, 2008
____________

Before TONI R. SCHEINER, DONALD E. ADAMS, and DEMETRA J.
MILLS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL

This appeal under 35 U.S.C. § 134 involves claims 1 and 46-53, the
only claims pending in this application. We have jurisdiction under 35
U.S.C. § 6(b).

Appeal 2008-1673
Application 10/631,573

INTRODUCTION
The claims are directed to a method of spectral karyotyping a
metaphase preparation of chromosomes. Claim 1 is illustrative:
1. A method of spectral karyotyping a metaphase preparation of
chromosomes, comprising the steps of:
(a) providing a metaphase preparation of chromosomes on a solid
support, wherein the preparation comprises more than one chromosome;
(b) combining said preparation with a plurality of semiconductor
nanocrystal conjugates, each of said conjugates being specific for a nucleic
acid molecule contained within each of said chromosomes, wherein each
semiconductor nanocrystal conjugate has an emission spectrum distinct from
the other semiconductor nanocrystal conjugates, wherein said combining is
performed under conditions that allow formation of complexes comprising
said conjugates and said nucleic acid molecule, when present;
(c) removing any unbound conjugate;
(d) detecting the presence of the complexes by monitoring a spectral
emission mediated by the semiconductor nanocrystal in the complex, to
provide a spectral karyotype.

The Examiner relies on the following prior art references to show
unpatentability:
Bruchez US 6,274,323 B1 Aug. 14, 2001
Thomas Ried et al., Simultaneous visualization of seven different DNA
probes by in situ hybridization using combinatorial fluorescence and
digital imaging microscopy,” 89 Proc. Natl. Acad. Sci. USA 1388-92
(1992).
E. Schröck et al., Multicolor Spectral Karyotyping of Human
Chromosomes, 273 Science 494-97 (1996).
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Marcel Bruchez Jr., et al., Semiconductor Nanocrystals as Fluorescent
Biological Labels, 281 Science 2013-16 (1998).

The rejection as presented by the Examiner is as follows:
Claims 1 and 46-53 stand rejected under 35 U.S.C. § 103(a) as being
unpatentable over the combination of Schröck, Ried and Bruchez.
We affirm.

DISCUSSION
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Therefore, we limit our discussion to
representative claims 1.
Claim 1 is directed to a method of spectral karyotyping a metaphase
preparation of chromosomes. The claimed method comprises four steps:
(a) providing a metaphase preparation of chromosomes, comprising
more than one chromosome, on a solid support;
(b) combining the chromosome preparation of step (a) with a plurality
of semiconductor nanocrystal conjugates;
(c) removing any unbound conjugate; and
(d) detecting the presence of the complexes by monitoring a spectral
emission mediated by the semiconductor nanocrystal in the complex, to
provide a spectral karyotype.
Step (b) of claim 1 places limitations on each semiconductor
nanocrystal conjugate. Specifically, each semiconductor nanocrystal
conjugate of step (b):
a. is specific for a nucleic acid molecule contained within each of said
chromosomes; and
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b. has an emission spectrum distinct from the other semiconductor
nanocrystal conjugates.
In addition, step (b) of claim 1 requires that the chromosome
preparation of step (a) is combined with a plurality of semiconductor
nanocrystal conjugates under conditions that allow formation of complexes
comprising the semiconductor nanocrystal conjugates and the nucleic acid
molecule contained within each of the chromosomes, when present.
Appellants do not dispute and therefore concede to the Examiner’s
finding that Schröck teaches every limitation of the claimed invention with
the exception of the use of a solid support and semiconductor nanocrystals
(Ans. 3-4).
With regard to the use of a solid support, the Examiner finds that
Schröck follows “the methodology of Reid . . . [which teaches the]
preparation of chromosomes on slides (Ans. 3). Appellants do not dispute
and therefore concede to the Examiner’s combination of Schröck and Reid.
With regard to the use of semiconductor nanocrystals, the Examiner
finds that Bruchez “teach[es] semiconductor nanocrystals which are used as
fluorescent labels” (Ans. 5). In addition, the Examiner finds that Bruchez
teaches that “[m]any sizes of nanocrystals may . . . be excited with a single
wavelength of light, resulting in many emission colors that may be detected
simultaneously” (id.). Further, the Examiner finds that Bruchez teaches that
“[o]ver repeated scans, the nanocrystal-labeled samples showed very little
photobleaching, far less than with conventional dye molecules” (Ans. 6).
Based on this evidence, the Examiner finds that “[i]t would have been
prima facie obvious to one of ordinary skill in the art at the time of the
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invention to have used the semiconductor nanocrystals of Bruchez et al. as
fluorescent labels in the spectral karyotyping method of Schrock” (Ans. 5).
In response, Appellants assert that “[t]he use of semiconductor
nanocrystals provides distinct advantages not contemplated in the prior art”
(App. Br. 71). Specifically, Appellants assert that a very large number of
chromosomal regions can be labeled simultaneously and “[t]he robustness of
semiconductor nanocrystals alleviates the problem of contamination
associated with degradation products encountered by organic dyes” (id.).
According to Appellants, “Schrock does not address the need for fluorescent
dyes with a wide range of tunable spectra” (id.). We note, however, that
“[i]n determining whether the subject matter of a patent claim is obvious,
neither the particular motivation nor the avowed purpose of the patentee
controls. What matters is the objective reach of the claim. If the claim
extends to what is obvious, it is invalid under § 103.” KSR Int’l Co. v.
Teleflex Inc., 127 S. Ct. 1727, 1741-42 (2007); see also In re Beattie, 974
F.2d 1309, 1312 (Fed. Cir. 1992) (“[T]he law does not require that the
references be combined for the reasons contemplated by the inventor.”).
Accordingly, we are not persuaded by Appellants’ argument.
Appellants assert that “[t]he Examiner alleges that a skilled artisan,
faced with no knowledge of the present invention, would be motivated based
on Schrock and Bruchez, to use unique, spectrally disparate dyes so that they
could avoid Schrock’s detection methods for deconvolution of emission
signals” (App. Br. 8). According to Appellants, “Schrock is directed to a

1 The Appeal Brief (App. Br.) is not paginated. Accordingly, we refer to
page numbers as if the App. Br. were numbered consecutively beginning
with the first page.
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detection method for deconvolution of emission signals. The Examiner’s
suggestion requires a substantial reconstruction and redesign of the elements
shown in the primary reference as well as a change in the basic principle
under which the primary reference construction was designed to operate”
(App. Br. 9). In addition, Appellants assert that “at the time of filing,
semiconductor nanocrystals were a new and fairly unconventional dye . . . .
it is unlikely that one would be motivated, based on Bruchez, to use a new
and fairly unconventional dye (at the time of filing), for the purpose of
avoiding emission overlap, despite Schrock’s insistence upon the use of
conventional dyes with overlapping emission spectra” (id.). We disagree.
As the Examiner explains, Schröck
provides a method in which combinations of five different
fluorophores were used to label 24 probes, which were then
used to stain metaphase chromosomes . . . . The method relies
on using a custom-built filter set and software which provides
Fourier transform-based spectral deconvolution . . . . Further,
even though dyes with spectral overlap can be used, the overlap
cannot be smaller than 15 nm . . . . In summary, this method
presents a significant investment of time and resources.
Therefore, one of ordinary skill in the art would look for a
simpler solution. Such a solution is presented by Bruchez.

(Ans. 6-7.) In this regard, the Examiner finds that Bruchez teaches
“Semiconductor nanocrystals were prepared for use as
fluorescent probes in biological staining and diagnostics.
Compared with conventional fluorophores, the nanocrystals
have a narrow, tunable, symmetric emission spectrum and are
photochemically stable. The advantages of the broad,
continuous excitation spectrum were demonstrated in a dual-
emission, single-excitation labeling experiment on mouse
fibroblasts. These nanocrystal probes are thus complementary
and in some cases may be superior to existing fluorophores.”

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(Ans. 7.)
As the Examiner points out, Bruchez refers to Schröck’s teaching that
combinatorial labeling has been used to generate 24 falsely
colored probes for spectral karyotyping (2). Conventional dye
molecules impose stringent requirements on the optical system
used to make these measurements; their narrow excitation
spectrum makes simultaneous excitation difficult in most cases,
and their broad emission spectrum with a long tail at red
wavelengths . . . introduces spectral cross talk between different
detection channels, making quantitation of the relative amounts
of different probes difficult. Ideal probes for multicolor
experiments should emit at spectrally resolvable energies and
have a narrow, symmetric emission spectrum, and the whole
group of probes should be excitable at a single wavelength (3,
4).

(Id.)
From this the Examiner reasons
one of ordinary skill in the art . . . would be motivated to accept
the solution to cumbersome and complicated spectral labeling
of Schrock et al. by replacing the fluorescent labels with
semiconductor nanocrystals, as using the semiconductor
nanocrystals would allow him/her to use already existing
equipment. Ample motivation to do this is provided in
Bruchez.

(Ans. 8.) We find no error in the Examiner’s analysis. “When a work is
available in one field of endeavor, design incentives and other market forces
can prompt variations of it, either in the same field or a different one. If a
person of ordinary skill can implement a predictable variation, § 103 likely
bars its patentability.” KSR, 127 S. Ct. 1727 at 1396. We disagree with
Appellants’ intimation that a person of ordinary skill in this art would not
have had a reasonable expectation of success simply because semiconductor
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nanocrystal technology was “a new and fairly unconventional dye” as of
Appellants’ filing date (App. Br. 9).
Further, for the reasons provided by the Examiner (Ans. 8-9), we
disagree with Appellants’ assertion that the modification of Schröck with the
teachings of Bruchez would require a substantial reconstruction and redesign
of Schröck (App. Br. 9). As the Examiner explains “the same basic
principles of fluorescence detection apply in both cases: excite the
fluorophore, measure emitted light. Thus, no change of principle of the
operation applies here, only simplification of the excitation and detection
processes from the method of Schrock” (Ans. 9).
We also disagree with Appellants' statement that the combination of
references relied upon by the Examiner “teach away from each other” (App.
Br. 10). A reference is said to “teach away” from a claimed invention when
it “suggests that the line of development flowing from the reference’s
disclosure is unlikely to be productive of the result sought by the applicant”
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). For the reasons set forth by
the Examiner (Ans. 6-9) the preponderance of evidence on this record fails
to support Appellants’ position.
On reflection, we find that the preponderance of evidence on this
record supports the Examiner’s conclusion that claim 1 is prima facie
obvious in view of the combination of Schröck, Ried and Bruchez.
Accordingly, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
being unpatentable over the combination of Schröck, Ried and Bruchez.
Claims 46-53 fall together with claim 1.

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CONCLUSION
In summary, we affirm the rejection of record.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 CFR § 1.136(a).

AFFIRMED

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